We propose to continue the follow-up of 51,529 male health professionals, aged 40 to 75 years in 1986, to address a series of dietary hypotheses related to cancers of the large bowel, prostate, lung, and melanoma. We have documented substantial variation in intake of a wide variety of nutrients in this population as well as the ability of our dietary questionnaire, administered in 1986, 1990, and 1994, to capture this variation. Response to biennial follow-up questionnaires has been at least 94%. In 1987 we collected data on waist and hip circumferences, which will be updated in 1996. In 1994 we collected, and stored in liquid nitrogen, plasma and DNA specimens from 18,000 participants. Analyses conducted during the current funding period have contributed importantly to several long-standing hypotheses regarding cancers of the colon and prostate, and have also suggested several new and promising directions. Our proposed specific aims build upon, extend, and refine observations we have already made, in part using the biological specimens to address a series of potential gene-diet interactions. During the proposed follow-up we anticipate a total of 607 cases of large bowel cancer and 2164 cases of prostate cancer. With this data we will be able to examine longer induction periods (which are likely to be particularly important for colon cancer), compute relatively precise estimates of effects, and examine potential nutrient-nutrient interactions. The availability of diet record data in a cohort subsample and statistical methods developed by our group allow the computation of relative risk estimates and confidence intervals corrected for measurement error. The repeated measurements of diet, not available in any other large cohort of men, will allow an assessment of the relation of longterm dietary intakes and change in diet to risks of important cancers in men.